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BACKGROUND: Patients with autoimmune hepatitis (AIH) and primary or autoimmune sclerosing cholangitis are at nutritional risk; their body composition and has not been extensively studied. We aimed to describe their body composition and identify clinical links. METHODS: Using magnetic resonance imaging (MRI), two reviewers segmented total psoas muscle area (tPMSA), visceral fat area (VFA) and subcutaneous fat area (mm(2)) and measured visceral and subcutaneous thickness (mm). Clinical, laboratory and quality of life (QoL; using PedsQL) data were collected. Sarcopenia was defined as tPMSA ≤5th percentile. Analysis of variance, Wilcoxon rank test and multivariable modelling were performed. A paediatric cohort with non-alcoholic fatty liver disease (NAFLD) was used as a comparator following propensity score matching. RESULTS: Fifty-eight patients with autoimmune liver disease (AILD) (33 [57%] with AIH) were included: median age 16 years (interquartile range [IQR]: 13-18), 33 (57%) male. Median time from diagnosis to MRI was 15 months (IQR: 2-39 months). Two patients (3%) had a BMIz indicative of mild malnutrition. tPMSA was measurable in 52 subjects (90%). Of those, 25 (48%) had sarcopenia. Sarcopenic patients had a lower blood urea nitrogen compared to non-sarcopenic (median [IQR]: 9.5 [8.0, 12.0] vs 11 [10, 14] mg/dL; P = .023). There was no difference in corticosteroid use between groups. The VFA of sarcopenic patients was higher (3156 [2064, 7492]) vs 2084 [688, 3092]) mm(2); P = .005). Patient-reported QoL negatively associated with VFA and general health negatively associated with VFA. Compared with NAFLD, the odds ratio for sarcopenia with AILD was 14.5 (95% confidence interval: 2.3-90.7). CONCLUSION: In autoimmune liver diseases, sarcopenia is highly prevalent, associated with increased visceral fat and QoL.

Delivery of adequate nutrition after liver transplantation (LT) surgery is an important goal of postoperative care. Existing guidelines recommend early enteral nutrition after abdominal surgery and in the child who is critically ill but data on nutritional interventions after LT in children are sparse. We evaluated the impact of a standardized postoperative feeding protocol on enteral nutrition delivery in children after LT. Data from 49 children (ages 0-18 years) who received a LT prior to feeding protocol implementation were compared with data for 32 children undergoing LT after protocol implementation. The 2 groups did not differ with respect to baseline demographic data. After protocol implementation, enteral nutrition was started earlier (2 versus 3 days after transplant; P = 0.005) and advanced faster when a feeding tube was used (4 versus 8 days; P = 0.03). Protocol implementation was also associated with reduced parenteral nutrition use rates (47% versus 75%; P = 0.01). No adverse events occurred after protocol implementation. Hospital length of stay and readmission rates were not different between the 2 groups. In conclusion, implementation of a postoperative nutrition protocol in children after LT led to optimized nutrient delivery and reduced variability of care.

To investigate the prevalence and characteristics of children with nonalcoholic fatty liver disease (NAFLD) who reduce their body mass index (BMI) z-score (BMIz) by.25, a goal in obesity medicine, and to determine the BMIz decrease needed for serum aminotransferase normalization.This retrospective, single-center study included patients aged18 years followed for NAFLD. Patients who had undergone weight loss surgery or had other reasons for weight loss/gain were excluded. Logistic regression was used to determine the odds of achieving a BMIz change of-.25, as well as predictors of this outcome.Of the 784 children who met the study criteria (median age, 13 years; 66% male; 24% Hispanic), 541 had a lowest BMIz at90 days following the baseline clinic visit. Of these children, 168 (31%) had a BMIz change of-.25 from baseline over a median of 367 days (IQR, 201-678 days). Decreases in serum aminotransferase and lipid levels were seen in both groups (with and without a BMIz change of-.25); however, these decreases were more pronounced in children who achieved a BMIz drop of.25. Hemoglobin A1c concentration did not change in either group. Young age (OR, .861; 95% CI, .81-.92; P .01) and non-Hispanic ethnicity (OR of non-Hispanic vs Hispanic, .61; 95% CI, .38-.97; P .04) were predictors of a BMIz change -.25. The BMIz decrease associated with normalization of serum alanine aminotransferase was .27.A BMIz reduction of.25 is associated with significant changes in serum aminotransferase levels. These findings can further guide the clinical management of children with NAFLD.

Global childhood obesity increased more than 8-fold over 40 years, inducing a very large personal, societal, and economic burden. Effects of available treatments are less than satisfactory; therefore, effective prevention is of high priority. In this narrative review, we explore preventive opportunities. The available evidence indicates large benefits of improving nutrition and lifestyle during early life, such as promoting breast-feeding and improving the quality of infant and early childhood feeding. Promoting healthy eating patterns and limiting sugar-containing beverage consumption from early childhood onwards are of great benefit. Regular physical activity and limited sedentary lifestyle and screen time alone have limited effects but are valuable elements in effective multicomponent strategies. The home environment is important, particularly for young children, and can be improved by educating and empowering families. School- and community-based interventions can be effective, such as installing water fountains, improving cafeteria menus, and facilitating regular physical activity. Reducing obesogenic risk factors through societal standards is essential for effective prevention and limiting socioeconomic disparity; these may comprise food, drink, and physical activity standards for day cares and schools, general food quality standards, front-of-pack food labeling, taxation of unhealthy foods, restriction of food advertisements to children, and others. Effective prevention of childhood obesity is not achieved by single interventions but by integrated multicomponent approaches involving multiple stakeholders that address children, families, and societal standards. Pediatricians and their organizations should be proactive in supporting and empowering families to support their children's health, and in promoting societal measures that protect children.

Objective The aim of the study was to assess the body composition of children with inflammatory bowel disease (IBD) and to study the accuracy of clinically available tools in predicting excess body fatness. We aimed at also exploring the influence of adiposity on pharmacokinetics during early Infliximab exposure. Methods Prospective cohort study in 5- to 17-year-old children with IBD initiating Infliximab therapy. Patient demographic, phenotypic, and laboratory data at the time of Infliximab initiation were recorded. Body composition was assessed using air displacement plethysmography (ADP). fat mass index (FMI = fat mass [kg]/(height [m])) was calculated to determine excess adiposity (defined as FMI ≥75th centile). Anthropometrics (weight, height, mid upper arm circumference [MUAC] and triceps skin fold thickness [TSF]) were obtained and MUAC and TSF measurements were used to calculate arm fat area (AFA) and arm muscle area z-scores. Statistical analysis was applied as appropriate. Results Fifty-three (68% male; 55% Crohn disease [CD], 45% ulcerative colitis [UC], median [IQR] age 15 [13-16] years) children with IBD were included. Twenty-four percentage of children with IBD (21% CD, 29% UC) had excess adiposity. Four children (31%) with FMI ≥75th centile were not identified by body mass index (BMI) alone (kappa of 0.60), and 2 children (15%) were not identified by AFA z-score alone. The intra- and interobserver reliability of MUAC and TSFT measurements was excellent. There was no difference in Infliximab trough levels at the end of induction between those with FMI less than or ≥75th centile. Conclusions Excess adiposity affects approximately 1 in 4 young patients with IBD and can be missed by routine obesity screening. Our exploratory study did not raise concerns of underexposure to infliximab in those children with excess adiposity during early drug exposure.

BACKGROUND & AIMS: A subset of patients with non-alcoholic steatohepatitis (NASH) respond to treatment with vitamin E. The characteristics of responders are not known. The objective of this study was to investigate the outcomes of vitamin E use in clinical practice and to determine factors associated with response to treatment. METHODS: A pediatric cohort with NASH treated with vitamin E for 6–24 months was studied retrospectively. Vitamin E response was defined as serum alanine aminotransferase (ALT) normalization or >50% ALT reduction from baseline. Univariate and multivariate backward logistic regression was used to determine the clinical, biochemical and histologic predictors of response to vitamin E. Available paired liver biopsy data were analyzed to determine histologic response. RESULTS: Of the 151 children prescribed vitamin E, 73 met inclusion/exclusion criteria. Of those 28 (38%) were vitamin E responders. Higher baseline serum alkaline phosphatase (ALP) levels, steatosis grade and NAFLD Activity Score (NAS) were associated with response to vitamin E (ALP: odds ratio (OR), 14.1; 95% confidence interval (CI), 1.7–118.6; steatosis: OR 2.5, 95%CI, 1.2–5.0; NAS: OR 1.6, 95%CI, 1.1–2.4). In a multivariate stepwise logistic regression model, ALP and steatosis grade rendered an area under the curve of 0.75 (p

Ventricular assist devices (VADs) support children with heart failure. The objective is to report on the nutrition outcomes of children requiring VAD.This was a retrospective study performed in a tertiary care center. All patients undergoing VAD placement from 2010 to 2018 were included. Exclusion criteria were VAD placement in outside hospitals, missing baseline anthropometrics, and death in the first 15 days post-VAD. Clinical, demographic, and nutrition data were collected from baseline and at 2 months post-VAD. Descriptive statistics were used.Of the 52 patients who had undergone VAD placement, 49 (65% male, 80% with cardiomyopathy; median age at VAD, 8 years) met the study criteria. The median length of stay following VAD was 63 days. Eight patients (16%) had malnutrition at baseline (five mild, two moderate, and one severe). At 2 months post-VAD, seven (of 49) patients had undergone heart transplantation and three (6%) were deceased. The proportion of patients with malnutrition was significantly different at 2 months post-VAD (P = 0.009), with six patients showing evidence of malnutrition (three mild, two moderate, and one severe; body mass index z score at baseline vs 2 months: 0.11 (± 1.72) vs 0.43 (± 0.94), P = 0.049). The percent of required energy consumed increased from 77% at baseline to 90% at 2 months post-VAD (P = 0.021). The proportion of patients fed solely enterally also increased (62% vs 84%, respectively; P = 0.042).VADs are associated with improved nutrition outcomes. Future studies should investigate the impact of VADs on body composition and longer-term outcomes.

To date, no pharmacotherapy exists for pediatric NAFLD. Losartan, an angiotensin II receptor blocker, has been proposed as a treatment due to its antifibrotic effects.The Nonalcoholic Steatohepatitis Clinical Research Network conducted a multicenter, double-masked, placebo-controlled, randomized clinical trial in children with histologically confirmed NAFLD at 10 sites (September 2018 to April 2020). Inclusion criteria were age 8-17 years, histologic NAFLD activity score ≥ 3, and serum alanine aminotransferase (ALT) ≥ 50 U/l. Children received 100 mg of losartan or placebo orally once daily for 24 weeks. The primary outcome was change in ALT levels from baseline to 24 weeks, and the preset sample size was n = 110. Treatment effects were assessed using linear regression of change in treatment group adjusted for baseline value. Eighty-three participants (81% male, 80% Hispanic) were randomized to losartan (n = 43) or placebo (n = 40). During an enrollment pause, necessitated by the 2019 coronavirus pandemic, an unplanned interim analysis showed low probability (7%) of significant group difference. The Data and Safety Monitoring Board recommended early study termination. Baseline characteristics were similar between groups. The 24-week change in ALT did not differ significantly between losartan versus placebo groups (adjusted mean difference: 1.1 U/l; 95% CI = -30.6, 32.7; p = 0.95), although alkaline phosphatase decreased significantly in the losartan group (adjusted mean difference: -23.4 U/l; 95% CI = -41.5, -5.3; p = 0.01). Systolic blood pressure decreased in the losartan group but increased in placebo (adjusted mean difference: -7.5 mm Hg; 95% CI = -12.2, -2.8; p = 0.002). Compliance by pill counts and numbers and types of adverse events did not differ by group.Losartan did not significantly reduce ALT in children with NAFLD when compared with placebo.

BACKGROUND An increasing number of clinical practice guidelines recommend screening children with obesity for non-alcoholic fatty liver disease (NAFLD). However, there is limited evidence regarding what parameters should be used to initiate the screening. OBJECTIVE The objective of this study was to determine whether obesity class rather than age group can identify a higher percent of children at risk of NAFLD as assessed by abnormal alanine aminotransferase (ALT). METHODS This is a cross-sectional study in a regional referral clinic for evaluation of obesity. Children were stratified by age group or by obesity class, and data obtained at first visit were analysed. RESULTS Of the 784 children, 482 were ≥10, 209 were 6 to 9 and 93 were 2 to 5 years of age. Abnormal ALT was observed in 32.1%, 46.9% and 61.0% of children with class I, II or III obesity, respectively (p

OBJECTIVES The aim of the study was to determine whether pediatric patients with nonalcoholic fatty liver disease (NAFLD) exposed to psychotropic medications have more severe liver disease compared to their counterparts who are not on these medications. We hypothesize that use of psychotropic agents is associated with liver disease severity. METHODS Children and adolescents with biopsy-confirmed NAFLD were included in this study. Histology data, detailed clinical information, and results of serum biochemistries performed within 3 months of the liver biopsy were collected retrospectively. Univariate and multivariate modeling was used to determine differences between the groups and to control for confounders. RESULTS A total of 228 patients were included, 17 (8%) of whom where on psychotropic medications at the time of the liver biopsy. Patients on psychotropic medications were more likely to also be on metformin (53% vs 18%, P

Serum immunoglobulin A (IgA) is a biomarker of liver disease severity in adult nonalcoholic fatty liver disease (NAFLD). The objective of this study was to assess whether this is true in pediatric NAFLD. This was a retrospective study of children followed in the Steatohepatitis Center of a tertiary care center (2010-2017). Serum IgA levels, histology and biochemical markers of hepatocellular injury and metabolic dysregulation were collected. Of the 600 children with available serum IgA levels (mean age 14 ± 3 years, 62% boys, 80% non-Hispanic), IgA was elevated in 4%. The group with elevated IgA levels was younger and had a greater representation of Hispanic ethnicity compared with those with normal or low IgA. Body mass index and aminotransferases were not different between the groups. Histology was available for 170 children and was not different in those with elevated, normal and low IgA. In contrast to adults, serum IgA is not a biomarker of liver disease severity in pediatric NAFLD.

OBJECTIVE: To determine the relationship between bioelectrical impedance analysis (BIA) and magnetic resonance imaging (MRI) obtained measures of body composition in children with nonalcoholic fatty liver disease (NAFLD). METHODS: Youth with obesity and NAFLD who had BIA and abdominal MRI testing were included. BIA measured skeletal muscle mass (SMM), appendicular lean mass (ALM), trunk muscle mass (TMM), and percent body fat. MRI measured total psoas muscle surface area (tPMSA) and fat compartments. Univariate analysis described the relationship between BIA- and MRI-derived measurements. Multivariable regression analyses built a model with body composition measured via MRI. RESULTS: 115 patients (82 (71%) male, 38 (33%) Hispanic, median age14 years) were included. There was a strong correlation between tPMSA and SMM, ALM, and TMM (correlation coefficients [CCs]: 0.701, 0.689, 0.708, respectively; all P < .001). Higher SMM, ALM, and TMM were associated with higher tPMSA. This association remained after controlling for age, sex, ethnicity, type 2 diabetes mellitus status, and body mass index z-score. Total fat mass by BIA and MRI-determined total, subcutaneous, and intraperitoneal fat area correlated significantly (CCs: 0.813, 0.808, 0.515, respectively; all P < .001). In univariate regression, higher total fat mass by BIA was associated with increased total fat area and increased fat in each of the four regions measured by MRI. After controlling for confounders, the association between total fat mass by BIA and total fat area by MRI persisted. CONCLUSIONS: BIA measures of muscle and fat mass correlate strongly with MRI measures of tPMSA and fat areas in children with obesity and NAFLD.

OBJECTIVES: To determine the prevalence of alternative causes of liver disease in a cohort of youth with overweight and obesity undergoing evaluation for suspected nonalcoholic fatty liver disease (NAFLD). METHODS: Multicenter, retrospective cohort study of patients aged ≤18 years with overweight and obesity and evidence of elevated serum aminotransferases and/or hepatic steatosis on imaging, referred for suspected NAFLD to Cincinnati Children’s Hospital Medical Center (2009–2017) or Yale New Haven Children's Hospital (2012–2017). Testing was performed to exclude the following: autoimmune hepatitis (AIH), Wilson disease, viral hepatitis (B and C), thyroid dysfunction, celiac disease, α-1 antitrypsin deficiency, and hemochromatosis. RESULTS: A total of 900 children with overweight and obesity (63% boys, 26% Hispanic ethnicity) were referred, with a median age of 13 years (range: 2–18). Most had severe obesity (n = 666; 76%) with a median BMI z score of 2.45 (interquartile range [IQR]: 2.2–2.7). Median alanine aminotransferase level at presentation was 64 U/L (IQR: 42–95). A clinically indicated liver biopsy was performed in 358 children (40%) at a median of 6 months (IQR: 1–14) post initial visit; of those, 46% had confirmed nonalcoholic steatohepatitis. Positive autoantibodies were observed in 13% of the cohort, but none met criteria for AIH. Only 19 (2%) were found to have other causes of liver disease, with no cases of viral hepatitis or Wilson disease detected. CONCLUSIONS: In a large, multicenter cohort, the vast majority of children with overweight and obesity with presumed or confirmed NAFLD tested negative for other causes of liver disease. In contrast to a previous pediatric report, no patient was diagnosed with AIH.

OBJECTIVES: The objective of this study was to investigate the association between measures of body composition based on bioelectrical impedance analysis (BIA) and histologic severity of liver disease in a pediatric cohort with nonalcoholic fatty liver disease (NAFLD). METHODS: This was a cross-sectional study of patients < 20 y old with histologically confi(rmed NAFLD followed) in our Steatohepatitis Center from 2017 to 2019. Contemporaneous body-composition data were obtained using a multifrequency octopolar BIA device (InBody 370, InBody, Seoul, South Korea). BIA data collected were skeletal muscle mass, appendicular muscle mass, and percentage body fat. Skeletal and appendicular muscle mass were corrected for height (dividing by the square of height), generating their respective indices. Univariate linear and logistic regression, followed by multivariable logistic regression analyses, were used. RESULTS: Of the 79 children included (27% female, 73% male; 38% Hispanic; median age, 13 y; median body mass index Z-score, 2.43), the median NAFLD Activity Score was 4 (interquartile range, 3–5). In multivariable regression analyses, the skeletal muscle mass index was negatively associated with hepatic steatosis after controlling for confounders (odds ratio, 0.76; 95% confidence interval, 0.62–0.93). Similarly, the appendicular muscle mass index was negatively associated with severity of hepatic steatosis severity (odds ratio, 0.69; 95% confidence interval, 0.53–0.90). In contrast, percentage body fat was not associated with hepatic steatosis. NAFLD Activity Score, lobular inflammation, ballooning scores, and fibrosis stage were not associated with measures of body composition. CONCLUSIONS: There is an inverse association between BIA-based measures of muscle mass and severity of hepatic steatosis in children with NAFLD. BIA data could further inform clinical decision making in this context

Background Autoantibodies are frequently positive in adults with nonalcoholic fatty liver disease (NAFLD) without concurrent autoimmune hepatitis (AIH). The clinical significance of this is unknown in children. Objective To determine the prevalence of autoantibody positivity in pediatric NAFLD and to evaluate its association with disease severity. Methods Multicenter, retrospective study of patients ≤18 years of age with biopsy-confirmed NAFLD. Descriptive statistics were used and groups were compared using Wilcoxon-Mann Whitney or χ2 testing, and multivariable logistic regression was used for binary or ordinal outcomes. Results One hundred and thirty six patients with a median age of 14 years were included. The median body mass index Z-score was 2.5 (interquartile range 2.2, 2.6). Positive antinuclear antibody (ANA), anti-smooth muscle antibody (ASMA), anti-liver-kidney microsomal antibody, or any combination of autoantibodies were observed in 22%, 14%, 0%, and 33% of patients, respectively. The proportion of patients with a steatosis score ≥2 was significantly higher in those with positive ANA (P = .045). In the multivariable regression analysis, positive ANA was associated with increased odds of steatosis score ≥2 (odds ratio, 5.91; 95% confidential interval, 1.50-23.26), after controlling for potential confounders. No other significant histology differences were seen between the groups. Conclusions Positive ANA and ASMA are common in children with NAFLD; however, anti-LKM positivity is not. ANA positivity is associated with more severe steatosis.

BACKGROUND AND AIMS: Longitudinal studies on childhood predictors of Nonalcoholic Fatty Liver Disease (NAFLD) progression are lacking. The objective of this study was to determine whether baseline clinical or laboratory measures predict liver disease outcomes in a pediatric NAFLD cohort. METHODS: Retrospective study of patients with presumed NAFLD using baseline and follow up clinical and laboratory measures. Disease outcomes were defined using the mean serum alanine aminotransferase (ALT) levels from 24-36 months after first visit. Logistic regression assessed the relationship between ALT progression/regression and predictor variables. Multivariable regression determined the best model for predicting the ALT outcome. Markov process modeling explored the likelihood for a patient to transition between ALT states. RESULTS: 816 patients identified, 144 had sufficient data at 24-36 months and 567 had paired ALT data over any 12 month period. Regression was seen in 26%, while 30% progressed. No baseline clinical or laboratory measurements had significant effect on disease outcomes. Markov modeling demonstrated that subjects were more likely to remain in their baseline ALT group or to worsen, than to improve. CONCLUSIONS: Routinely obtained baseline clinical or laboratory measures cannot help risk-stratify youth with presumed NAFLD in terms of long-term outcomes. Close clinical, radiographic, and histologic evaluation of patients is warranted to determine those at risk of progression.

OBJECTIVES: To determine the prevalence of renal impairment in a large cohort of youths with histologically confirmed nonalcoholic fatty liver disease (NAFLD), and to determine its association with liver disease severity. STUDY DESIGN: Clinical, laboratory, and histology data were collected retrospectively in a pediatric cohort with biopsy-confirmed NAFLD at a tertiary care center between 2010 and 2017. Histological NAFLD severity was scored using validated criteria. Glomerular filtration rate (GFR) was calculated and categorized as low (136 mL/min/1.73 m(2)). Univariate and multivariate modeling were used to determine differences between the GFR groups and to control for confounders. RESULTS: The cohort comprised 179 patients (82% non-Hispanic; median age; 14 years; IQR, 12–16 years). One-third of the patients had abnormal renal function, including 36 (20%) with glomerular hyperfiltration and 26 (15%) with low GFR. In multivariable logistic regression, compared with normal GFR, hyperfiltration was independently associated with higher NAFLD activity score (aOR, 2.96; 95% CI, 1.49–5.87; P = .002), after adjusting for age, sex, ethnicity, obesity severity, presence of type 2 diabetes mellitus, and medications. CONCLUSIONS: In this large cohort with histologically confirmed NAFLD, renal impairment was highly prevalent and associated with liver disease severity, independent of obesity severity. Screening patients with confirmed NAFLD for renal complication is recommended.

Introduction and aim. This manuscript seeks to analyze the impact of lifestyle changes on body mass index (BMI), aminotransferases and steatosis in children and adolescents with nonalcoholic fatty liver disease (NAFLD). Material and methods. A review of PubMed, BIREME, Scopus, EMBASE, Medline and Web of Science databases 2015 was performed seeking studies addressing the impact of lifestyle interventions on children and/or adolescents with NAFLD. Inclusion were manuscripts written in Portuguese, English and Spanish, as well as age less than 18 years. Two reviewers performed the data extraction independently and differences were resolved by consensus. Outcome measures were BMI, serum aminotransferase levels and the presence of hepatic steatosis. Results. The literature search identified 71,012 articles. After excluding 46,397 duplicates and other clearly irrelevant studies, 89 publications were reviewed in detail. Another 55 studies were excluded at this stage. Subsequently, 18 were excluded due to lack of data and three new articles were found in the review of the references of previously identified manuscripts. Therefore, 19 studies that had evaluated 923 subjects (477 boys and 446 girls) aged 6-18 years were included in the review. In most studies, the intervention included aerobic exercise and diet. In nine studies, BMI improved significantly following the intervention. The vast majority of studies reported a benefit from the intervention on aminotransferase levels. Lifestyle changes also had a significant impact on steatosis, reducing the risk by 61%. Conclusion. In conclusion lifestyle changes lead to significant improvements in BMI, aminotransferase levels and hepatic steatosis in children and adolescents with NAFLD.

Lipid emulsions have been associated with liver injury. Newer mixed emulsions (ML), such as SMOFlipid (Fresenius Kabi, Germany), are thought to be more hepatoprotective than soybean-based emulsions (SL), such as Intralipid (Baxter). Pediatric studies comparing long-term use between the 2 are limited. This study compares the severity of hepatic injury between a prospective cohort of hospitalized children on ML (n = 20) and a historical age- and diagnosis-matched cohort of hospitalized children on SL (n = 20). Median exposure to ML and SL were 10 versus 6 weeks (P = 0.030), respectively, at similar median lipid doses (2.2 vs 2.1 g · kg · day). Using a generalized estimating equations approach, conjugated bilirubin trajectory was found to be lower in patients on ML compared with SL (P < 0.001), suggesting that prolonged exposure (≥4 weeks) to ML is associated with decreased liver injury compared with SL in hospitalized children.

To determine the prevalence of underreporting of hepatic steatosis found incidentally on computed tomography (CT).Retrospective cross-sectional study including patients18 years of age who had undergone unenhanced abdominal CT for evaluation of nephrolithiasis. Hepatic and splenic attenuation were measured independently by 2 reviewers. Hepatic steatosis was defined using various previously established criteria (4 original criteria designed to detect moderate/severe steatosis and 3 secondary criteria designed to identify mild steatosis). Radiology reports and clinical notes were reviewed for documentation of steatosis. Serum alanine aminotransferase levels were collected. Kappa statistics were used to assess agreement between reviewers.A total of 584 patients were included. Agreement between reviewers' measurements for categorical classification of presence of steatosis was excellent (kappa statistic agreement87%). The prevalence of hepatic steatosis ranged from 3% to 35%, depending on the criterion. Using absolute liver attenuation48 Hounsfield units (most likely reflective of the truth, given alanine aminotransferase distribution and body mass index data), the prevalence was 7% (n = 42). Steatosis was reported for only 12 of 42 (28%) of these patients and was documented in clinical notes in only 3 of those cases.Hepatic steatosis is underreported as an incidental finding of CT for nephrolithiasis. Given the prevalence and silent nature of nonalcoholic fatty liver disease, a high level of suspicion is needed, so as not to miss the opportunity to identify steatosis in childhood.

Background The literature on the optimal clinical management of pediatric patients with nonalcoholic fatty liver disease (NAFLD) is limited. The objective of this study was to identify discrepancies in the care provided to patients with NAFLD by hepatologists practicing in academic centers across Canada. Methods A nationwide survey was distributed electronically to all pediatric hepatologists practicing in university-affiliated hospitals using the infrastructure of the Canadian Pediatric Hepatology Research Group. The responses were anonymous. Results The response rate to the survey was 79%. Everyone reported diagnosing NAFLD based on a combination of elevated transaminases and imaging suggestive of steatosis in the context of an otherwise negative workup for other liver diseases. Only 14% use liver biopsy to confirm the diagnosis. There are significant discrepancies in the frequency of screening for other comorbidities (eg, hypertension, sleep apnea, etc) and in the frequency of laboratory investigations (eg, lipid profile, transaminases, international normalized ratio, etc). Frequency of outpatient clinic follow-up varies significantly. Treatment is consistently based on lifestyle modifications; however, reported patient outcomes in terms of body mass index improvements are poor. Conclusions There are significant discrepancies in the care provided to children with NAFLD by hepatologists practicing in academic centers across Canada.

BACKGROUND AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity. Obesity is associated with lower socioeconomic status (SES). An independent link between pediatric NAFLD and SES has not been elucidated. The objective of this study was to evaluate the distribution of socioeconomic deprivation, measured using an area-level proxy, in pediatric patients with known NAFLD and to determine whether deprivation is associated with liver disease severity. METHODS: Retrospective study of patients

BACKGROUND: Paediatric non-alcoholic fatty liver disease (NAFLD) is highly prevalent among children with obesity. The primary objective of this study was determining whether obesity severity is associated with NAFLD severity. By using paediatric classifications for severe obesity, clinicians may be able to better risk stratify patients, which in turn would guide more effective management and treatment. METHODS: Retrospective cohort study including patients followed at Cincinnati Children's Medical Center for NAFLD. Patients were categorized as overweight or class I, II, III obese based on established body mass index (BMI) cut-offs. Liver disease severity was determined using biochemical, imaging (magnetic resonance elastography [MRE]), and histologic evidence of liver injury. RESULTS: Three cohorts were studied individually based on the method used to assess disease severity (biochemical n = 767, imaging n = 366, and histology n = 249). Between the three cohorts, there were significant differences in age, proportion of patients with class II and class III obesity, and serum alanine transaminase (ALT) levels. In the biochemistry cohort, the odds of having ALT > 80 U/L were highest in patients with class III obesity (P = .026). In the imaging cohort, liver stiffness was significantly different between BMI groups of patients (P = .001). In the histology cohort, those with class III obesity had significantly higher odds of NAFLD activity score (NAS) ≥ 5 (P = .012). DISCUSSION: Obesity severity is associated with liver disease severity. Patients with more severe obesity are more likely to have more advanced liver disease, a finding that can assist in risk stratification, as well as monitoring and treatment approaches.

Chronic liver disease places patients at increased risk of malnutrition that can be challenging to identify clinically and treat. Nutrition support is a key aspect of the management of these patients as it has an impact on their quality of life, morbidity, and mortality. There are significant gaps in the literature regarding the optimal nutrition support for patients with different types of liver diseases and the impact of these interventions on long-term outcomes. This Position Paper summarizes the available literature on the nutritional aspects of the care of patients with chronic liver diseases. Specifically, the challenges associated with the nutritional assessment of these subjects are discussed, and recently investigated approaches to determining the patients' nutritional status are reviewed. Furthermore, the pathophysiology of the malnutrition seen in the context of chronic liver disease is summarized and monitoring, as well as treatment, recommendations are provided. Lastly, suggestions for future research studies are described.

BACKGROUND/OBJECTIVES: To determine associations between serum 25-hydroxyvitamin D (25(OH)-D) concentrations and histologic nonalcoholic fatty liver disease (NAFLD) severity. SUBJECTS/METHODS: Clinical, laboratory, and histology data were collected retrospectively in a pediatric cohort with biopsy-confirmed NAFLD. Serum 25(OH)-D concentrations were used to define vitamin D deficiency (≤20 ng/ml), insufficiency (21–30 ng/ml), and sufficiency (≥31 ng/ml). RESULTS: In all, 234 patients (78% non-Hispanic, median age 14 years) were included. The majority (n = 193) were either vitamin D insufficient (50%) or deficient (32%). Eighty-four patients (36%) reported taking vitamin D supplements at the time of biopsy; serum 25(OH)-D concentrations were not higher in those supplemented. There were no differences in the demographic, clinical, and laboratory characteristics of the three vitamin D status groups. Severity of steatosis, ballooning, lobular/portal inflammation, and NAFLD activity score were also not different between the groups. The proportion of patients with significant fibrosis (stage ≥ 2) was higher in those with insufficiency (29%) compared to those who were sufficient (17%) or deficient (15%, p = 0.04). After controlling for important covariates selected from age, body mass index, ethnicity, vitamin D supplementation, and season, the insufficient group had increased odds of a higher fibrosis score compared to the sufficient group (adjusted OR, 2.04; 95%CI, 1.02–4.08). CONCLUSIONS: Vitamin D deficiency and insufficiency are common in children with NAFLD, but not consistently related with histologic disease severity. Prospective longitudinal studies are needed to determine optimal dosing strategies to achieve sufficiency and to determine whether adequate supplementation has an impact on histology.

Question An overweight 12-year-old male patient with nonalcoholic fatty liver disease has had little improvement in liver steatosis or triglyceride levels over the past 2 years. Is omega-3 supplementation useful in managing his condition?

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is the most common pediatric chronic liver disease. Little is known about outcomes in recognized youth. METHODS: We compared paired liver biopsies from 122 of 139 children with NAFLD (74% male; 64% white; 71% Hispanic; mean age, 13 ± 3 years; age range, 8–17 years) who received placebo and standard of care lifestyle advice in 2 double-blind, randomized clinical trials within the nonalcoholic steatohepatitis (NASH) clinical research network from 2005 through 2015. We analyzed histologic changes with respect to baseline and longitudinal change in clinical variables using regression analysis. RESULTS: At enrollment, 31% of the children had definite NASH, 34% had borderline zone 1 NASH, 13% had borderline zone 3 NASH, and 21% had fatty liver but not NASH. Over a mean period of 1.6 ± 0.4 years, borderline or definite NASH resolved in 29% of the children, whereas 18% of the children with fatty liver or borderline NASH developed definite NASH. Fibrosis improved in 34% of the children but worsened in 23%. Any progression to definite NASH or in fibrosis occurred in 36% of the children, and both occurred in 11% of the children. Any improvement in NASH or fibrosis occurred in 52%, and both occurred in 20% of children. Type 2 diabetes developed in 5% of the cohort. Any progression to NASH and/or fibrosis was associated with adolescent age, higher waist circumference, levels of alanine or aspartate aminotransferase, total and low-density lipoprotein-cholesterol at baseline, increasing level of alanine aminotransferase, and hemoglobin A1C (P < .05). Progression to NASH and/or fibrosis were also associated with increasing level of gamma-glutamyl transferase and development of type 2 diabetes (P < .01). Increasing level of gamma-glutamyl transferase also associated with reduced odds of any improvement (P = .003). CONCLUSIONS: One-third of children with NAFLD enrolled in placebo groups of clinical trials had histologic features of progression within 2 years, in association with increasing obesity and serum levels of aminotransferases and loss of glucose homeostasis.

CV disease is a major cause of morbidity and mortality following solid organ transplantation in adults. While the prevalence of multiple cardiometabolic risk factors is increased in pediatric solid organ transplant recipients, it is not clear whether they have subclinical CV changes. cIMT, central pWV, and CAC are indicative of subclinical CV disease, and, in adults, predict future CV events. The objective of this systematic review and meta-analysis was to investigate the prevalence of subclinical CV changes, as measured by cIMT, pWV, and CAC among pediatric solid organ transplant recipients. We searched MEDLINE(®) and EMBASE and conducted meta-analysis for studies that evaluated cIMT, central pWV, and CAC among pediatric solid organ transplant recipients (kidney, lung, intestine and liver). The search identified nine eligible studies that included a total of 259 patients and 685 healthy controls. Eight studies reported on kidney transplant recipients and one study on a combined cohort of kidney and liver transplant recipients. The mean cIMT of transplant recipients was significantly higher than that of healthy controls (mean difference = 0.05 mm, 95% CI 0.02-0.07; p < 0.0001) with an estimated pooled prevalence of elevated cIMT of 56.0% (95% CI 17.0-95.0). The one study that assessed pWV showed increased vascular stiffness in transplant recipients compared to healthy controls. No studies assessing for CAC were found. There were limited data regarding subclinical CV disease following pediatric solid organ transplantation. In conclusion, kidney transplantation in childhood is associated with a higher prevalence of subclinical CV changes compared to healthy children. Longitudinal studies are needed to determine whether children have increased CV morbidity and mortality after transplantation.

Objective. Adult data suggest that frequent monitoring of patients with nonalcoholic fatty liver disease (NAFLD) may be associated with improved outcomes. The optimal frequency of outpatient visits for the management of pediatric NAFLD remains unknown. Study Design. In this retrospective study, two cohorts of patients with NAFLD, one followed on a yearly basis and one followed on 3-month intervals, were included. Both received similar advice regarding lifestyle changes. Primary outcome was change in BMI z-scores over a year. Secondary outcomes were the change in serum transaminases and markers of metabolic dysregulation. Results. Fifty-six patients were included (28 per group). The majority (71%) were male with a mean (±SD) age of 12.2 (±2.7) years. At baseline, there were no differences in BMI z-scores (2.8 versus 2.9; p=0.72) and ALT levels (101 versus 100 U/L; p=0.95) between the groups (yearly versus three-month, resp.). Twelve months later, those followed on a 3-month basis demonstrated a significant decrease in BMI (net BMI z-score change = −0.06; p=0.37), accompanied by a significant improvement in serum ALT (−25 U/L; p<0.01) and AST (−13 U/L; p=0.03) levels. There were no differences in fasting lipid profiles. Conclusion. Frequent clinic visits are associated with improved outcomes in pediatric NAFLD.

OBJECTIVE: To investigate the association between muscle mass and liver disease severity in pediatric patients with non-alcoholic fatty liver disease (NAFLD). STUDY DESIGN: This was a retrospective study of patients aged

Background The prevalence of non-alcoholic fatty liver disease (NAFLD) in children is 8% in the general population, and 34% in the context of obesity. There is a paucity of data on the prevalence of hepatic steatosis in healthy children in Ontario. Aims To determine the prevalence of hepatic steatosis using abdominal computed tomography (CT) scans in a cohort of previously healthy children across the paediatric age spectrum in Ontario, Canada, and to determine any association between measures of abdominal adiposity and hepatic steatosis. Methods Retrospective review of the SickKids Trauma Database from 2004-2015. Previously healthy children ages 1-17 years having undergone an abdominal CT scan as a part of routine trauma assessment were included, and those with an intra-abdominal injury excluded. Steatosis was defined as a difference between liver and spleen attenuation ≤-25HU. The percentage of the total area occupied by abdominal subcutaneous adipose and visceral adipose tissue was measured. Anthropometrics and baseline demographics were collected. Results A total of 503 (51% male) children with mean (±SD) age 9.5 ± 4.5 years and weight z-score of 0.37 ± 1.05 were studied. Seventy-seven (15%, 95% CI [12%-18%]) had hepatic steatosis; no differences found between sexes or across age quartiles. The abdominal subcutaneous adipose tissue area was greater in those with hepatic steatosis compared to those without (32% [22-42] vs 24% [17-36], P = 0.003). The visceral adipose tissue area was significantly greater in older children ≥9.8 years with hepatic steatosis (7.7% [5.1-10] vs 6.6% (4.9-8.5), P = 0.04). Conclusion Hepatic steatosis was highly prevalent in previously healthy children in Ontario, including children of pre-school age. We found an association between hepatic steatosis and abdominal subcutaneous adipose tissue, and in older children with visceral adipose tissue.

The provision of optimal nutritional care is based on accurate estimations of patients' resting energy expenditure. The latter can be calculated with the use of predictive equations or measured with indirect calorimetry (IC). Owing to their ease of use, mathematical equations have largely replaced IC in clinical practice. This article examines the limitations and predictive inaccuracy of commonly used equations in pediatrics, which may contribute to the provision of poor nutritional care and directly affect patient outcomes. In addition, the role of IC is discussed and the physiology of nutrient metabolism, in terms of energy expenditure, is reviewed.

Background Chronically ill children often require feeding via gastrostomy tubes (G-tubes). Commercial formula is most commonly used for enteral feeding; however, caregivers have been requesting blenderized tube feeds (BTFs) as an alternative. The objective of this study was to evaluate the feasibility of using BTFs in a medically complex pediatric population and assess their impact on clinical outcomes, as well as the microbiota. Methods Twenty pediatric participants were included. Participants were G-tube dependent and receiving ≥75% of their daily energy requirements from commercial formula. Over 4 weeks, participants were transitioned from commercial formula to BTF and were monitored for 6 months for changes in nutrient intake, gastrointestinal symptoms, oral feeding, medication use, and caregiver perceptions. Changes to intestinal microbiota were monitored by 16S rDNA-based sequencing. Results Transition onto BTF was feasible in 17 participants, and 1 participant transitioned to oral feeds. Participants required 50% more calories to maintain their body mass index while on BTFs compared with commercial formula. BTF micronutrient content was superior to commercial formula. Prevalence of vomiting and use of acid-suppressive agents significantly decreased on BTFs. Stool consistency and frequency remained unchanged, while stool softener use increased. The bacterial diversity and richness in stool samples significantly increased, while the relative abundance of Proteobacteria decreased. Caregivers were more satisfied with BTFs and unanimously indicated they would recommend BTFs. Conclusion Initiation and maintenance of BTFs is not only feasible in a medically complex pediatric population but can also be associated with improved clinical outcomes and increased intestinal bacterial diversity.

BACKGROUND Pediatric patients with nonalcoholic fatty liver disease (NAFLD) require targeted nutrition therapy that relies on calculating energy needs. Common energy equations are inaccurate in predicting resting energy expenditure (REE), influencing total energy expenditure (TEE) estimates. Equations based on allometric scaling are simple, accurate, void of subjective activity and/or stress factor bias, and they estimate TEE. OBJECTIVE To investigate the predictive accuracy of an allometric energy equation (AEE) in predicting TEE of children and adolescents with NAFLD. METHODS Retrospective study performed in a single institution. The allometric equation was used to calculate AEE, and the results were compared with TEE calculated using indirect calorimetry data (measured REE) multiplied by an activity factor (AF) of 1.5 or 1.7. RESULTS Fifty-six patients with a mean age of 13 years were included in this study. The agreement between TEE (using an AF of 1.5) and AEE was -96 kcal/d (confidence interval, -29 to 221). The predictive accuracy of the allometric equation was not different between obese and nonobese patients. CONCLUSIONS Allometric equations allow for accurate estimation of TEE in children with NAFLD.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in children. The phenotype of NAFLD varies widely, and non-invasive predictors of disease severity are scarce and are needed to tailor clinical management.We compared liver fibrosis by histology with proposed non-invasive predictors of fibrosis, including alanine transaminase (ALT), aspartate transaminase (AST), AST/ALT ratio, AST to platelet ratio index, fibrosis-4, paediatric NAFLD fibrosis index and paediatric NAFLD fibrosis score.The area under the curve of scores obtained while predicting fibrosis in children with NAFLD ranged from 0.51 to 0.67.The tested non-invasive fibrosis scoring systems, some of which were originally designed for adult populations, did not adequately predict fibrosis in a paediatric cohort. Further development of risk prediction scores in children are needed for the management of paediatric patients and will likely need to be developed within a large paediatric data set in order to improve specificity and sensitivity.

Background Malnutrition is common among congenital diaphragmatic hernia (CDH) survivors and may result from elevated respiratory effort. We evaluated body mass index (BMI), measured resting energy expenditure (mREE) and pulmonary function test (PFT) results in children and adolescents with CDH to determine if there is a correlation. Methods With ethics approval (REB# 1000035323), anthropometrics, indirect calorimetry (IC) results and PFTs were collected from patients 5–17years of age during CDH clinic visits between 2000 and 2016. Malnutrition was defined as BMI z-scores Results & discussion Of 118 patients who attended clinic, 33 had reproducible PFTs, anthropometrics and IC results. Mean BMI z-score was −0.89±1.47 and 24% of patients were malnourished; mean FVC z-score (−1.32±1.39) was within normal range, whereas mean z-scores for FEV 1 (−2.21±1.68) and FEV 1 /FVC ratio (−1.78±0.73) were below normal. A correlation was noted between BMI and PFTs (FEV 1 r=0.70, P 1 (r=0.10, P=0.57); or FVC (r=0.28, P=0.12). Conclusions These preliminary results suggest that a correlation is present between BMI and lung function in CDH children and adolescents, whereas lung function does not seem to correlate with mREE. Level of evidence II.

Background The mainstay of treatment for pediatric nonalcoholic fatty liver disease (NAFLD) is lifestyle modification, which includes dietary changes that lead to slow but sustained weight loss or weight stabilization in growing children. Accurate estimation of energy requirements is necessary to achieve this goal. The objective of this study was to assess the accuracy of the most commonly used equations in predicting the resting energy expenditure (REE) of children with NAFLD. Methods This was a retrospective study performed in a single institution. The predictive accuracy of various equations was assessed by comparing their estimates against the measured REE obtained with indirect calorimetry. Accuracy was defined as an estimate within 10% of measured REE. Results Fifty-six children (70% male; 52% white and 36% Asian) with a median age of 13 years were included. The median measured REE was 1829 kcal/d. Of the equations studied, the Schofield had the smallest average bias (-32 kcal/d; confidence interval, -121 to 56). The Schofield and Molnar equations were the most accurate, providing REE estimates within 10% of measured in 59% of cases. The remaining equations had lower and variable predictive accuracy. The use of adjusted body weight in predictive equations did not improve the predictive accuracy. Conclusion In a cohort of children and adolescents with NAFLD, the Schofield and Molnar equations performed best in predicting energy expenditure. However, predictive equations were often inaccurate, suggesting that clinicians should interpret their results with caution and consider using indirect calorimetry when available.

Objective Health related quality of life (HRQL) of children using medical technology at home is largely unknown. Our aim was to examine the HRQL in children on long-term ventilation at home (LTHV) in comparison to a cohort using an enterostomy tube. Study Design Participants were divided into three groups: 1) LTHV without an enterostomy tube (LTHV cohort); 2) Enterostomy tube (GT cohort); 3) LTHV with an enterostomy tube (LTHV+GT cohort). Caregivers of children ≥ 5 years and followed at SickKids, Toronto, Canada, completed three questionnaires: Health Utilities Index 2/3 (HUI2/3), Caregiver Priorities Caregiver Health Index (CPCHILD), and the Paediatric Quality of Life Inventory (PedsQL). The primary outcome was the difference in utility (HUI2/3) scores between the cohorts. Results One hundred and nineteen children were enrolled; 47 in the LTHV cohort, 44 in the GT cohort, and 28 in the LTHV+GT cohort. In univariate analysis, HUI2 mean (SE) scores were lowest for the GT cohort, 0.4 (0.04) followed by the LTHV+GT, 0.42 (0.05) and then the LTHV cohort, 0.7 (0.04), p = 0.001. A similar trend was seen for the HUI3 mean (SE) scores: GT cohort, 0.1 (0.06), followed by the LTHV +GT cohort, 0.2 (0.08) and then the LTHV cohort, 0.5 (0.06), p = 0.0001. Technology cohort, nursing hours and the severity of health care needs predicted HRQL as measured by the HUI2/3. Conclusion The HRQL of these children is low. Children on LTHV had higher HRQL than children using enterostomy tubes. Further work is needed to identify modifiable factors that can improve HRQL.

Malnutrition is common in children with end-stage liver disease (ESLD) and is associated with increased morbidity and mortality. The inability to accurately estimate energy needs of these patients may contribute to their poor nutrition status. In clinical practice, predictive equations are used to calculate resting energy expenditure (cREE). The objective of this study is to assess the accuracy of commonly used equations in pediatric patients with ESLD.Retrospective study performed at the Hospital for Sick Children. Clinical, laboratory, and indirect calorimetry data from children listed for liver transplant between February 2013 and December 2014 were reviewed. Calorimetry results were compared with cREE estimated using the Food and Agriculture Organization/World Health Organization/United Nations University (FAO/WHO/UNU), Schofield [weight], and Schofield [weight and height] equations.Forty-five patients were included in this study. The median age was 9 months, and the most common indication for transplantation was biliary atresia (64%). The Schofield [weight and height], FAO/WHO/UNU, and Schofield [weight] equations were compared with indirect calorimetry and found to have a mean (SD) difference of 48.8 (344.0), 59.3 (229.8), and 206.5 (502.6) kcal/d, respectively. The FAO/WHO/UNU, Schofield [weight], and Schofield [weight and height] equations introduced a mean error of 21%, 38%, and 76%, respectively. The FAO/WHO/UNU equation tended to underestimate, whereas the Schofield equations overestimated the REE.Commonly used predictive equations perform poorly in infants and young children with ESLD. Indirect calorimetry should be used when available to guide energy provision, particularly in children who are already malnourished.

Fatty liver disease in children has been increasingly recognized as an important pediatric health problem over the last 2 decades. Obesity is strongly associated with nonalcoholic fatty liver disease (NAFLD), with high rates of NAFLD reported among obese cohorts, and even higher rates among morbidly obese adolescents. 1,2 Data from multiple sources, including the US National Health and Nutrition Examination Survey (NHANES), suggest the overall prevalence of children suspected to have NAFLD has more than doubled in the last 2 decades. 3-5 The prevalence of pediatric NAFLD may be as high as 9.6% in the general population, 6 and NAFLD is now the most common cause of chronic pediatric liver disease in the developed world and is increasing in prevalence across the developing world as well. 7-11 The primary care provider is at the forefront of this epidemic of childhood obesity and will see many children at risk for NAFLD. Given their frontline status, the primary care provider has the potential to both detect and intervene in the natural history of childhood NAFLD. NAFLD is not a single entity but reflects a series of disease states across a spectrum of severity. These distinctions have been established based on histologic definitions wherein NAFLD is the umbrella diagnosis, with a threshold of macrovesicular steatosis being present in $5% of hepatocytes, and nonalcoholic steatohepatitis (NASH) is the severe subset of patients on the NAFLD spectrum wherein the liver histology has inflammation and cellular injury with or without fibrosis in addition to the steatosis. 12 The long-term prognosis for children with NAFLD is determined by the liver histology at diagnosis; specifically, whether they have the mildest form (isolated hepatic steatosis) or the more severe form, NASH. These distinctions are not merely semantics, as NASH-related fibrosis can progress to cirrhosis as early as childhood. 13 We now understand that all-cause mortality and liver transplant free survival are different in patients with NASH compared with individuals with steatosis alone or the non-NAFLD background population. 14,15 Over the pastdecade, thescientificcommunityhas garneredstrongevidence implicating NASH as a key contributor in the development and severity of extrahepatic comorbidities of the metabolic syndrome. 16-19 Under the guidance of the North American Society’s Pediatric Gastroenterology Hepatology and Nutrition Foundation’s NAFLD initiative, we constituted an expert group of pediatric gastroenterologistsfromacrossthe USand Canada with acommonresearch andclinicalfocusinNAFLD.Theauthorsofthisreport areall members of this Expert Committee on NAFLD and aim to provide the readership insight into recent advances in the field of pediatric NAFLD, dispel common misconceptions regarding the use of alanine aminotransferase (ALT) in NAFLD, and highlight existing knowledge gaps in identification and assessment of children with NAFLD, as well as research. Thecontentsofthisreport donotrepresenttheofficial guidelines of North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

Failure to thrive (FTT) is well documented among congenital diaphragmatic hernia (CDH) survivors ≤3years of age, but its etiology, severity, and persistence beyond this age require further elucidation.We conducted a single-center, retrospective study assessing anthropometrics, measured energy expenditure, and feeding tube (FT) use of 5-17 year olds in our multidisciplinary CDH clinic since January 2001. We stratified clinic visits based on age A: 5.0-6.9, B: 7.0-9.9, C: 10.0-14.9, and D: 15-17.9years.One hundred sixteen patients with 376 outpatient visits were reviewed. Anthropometric z-scores were below zero and did not vary across age cohorts. FTT and growth stunting each occurred in 14% of clinic visits. FTs inserted during infancy occurred in 25% of patients, and 60% remained by age 7years. In cohort A, those with FTs were lighter and shorter than those without (p0.05) but had similar BMIs. FTT incidence was higher in the FT group (p=0.020), but FTs were present in only 30% of those with FTT. Indirect calorimetry revealed increased energy expenditure in 58% of patients.Failure to thrive continues in long-term CDH survivors, FTs may not improve incidence of FTT. Increased energy expenditure may play a role.

UNLABELLED PTMS describes the presence of ≥3 cardiometabolic risk factors that include obesity, hypertension, dyslipidemia, and IR. The prevalence of the clustering of ≥3 cardiometabolic risk factors or central obesity has not been studied in pediatric LT recipients. Single-center, cross-sectional study. INCLUSION CRITERIA LT recipients 2-18 yr-old, at least one yr post-LT. EXCLUSION CRITERIA recipients of liver retransplants or multivisceral transplants. Eighty-seven patients were identified. Median age was 9.8 yr (range 2-18), median time since LT was 6.9 yr (range 1-17). The most common indication for LT was biliary atresia (56%), and the most frequently used immunosuppressant was tacrolimus (80%). The prevalence of overweight and obesity was 21% and 5%, respectively. Central obesity affected 14%, hypertension 44%, IR 27%, low HDL 20%, and hypertriglyceridemia 39% of patients. The prevalence of ≥3 cardiometabolic risk factors was 19%. Fifty percent of the overweight/obese patients had ≥3 risk factors. Time since transplant, immunosuppression and renal function were not different between those with

Renal impairment is frequently compromised in patients with end-stage liver disease and is associated with increased long-term mortality post-LT. In contrast to CNI, basiliximab is an immunosuppressive agent with minimal nephrotoxic potential. This study reviews the experience of a single pediatric liver transplant center's renal-sparing approach with the use of basiliximab and MMF to compensate for delayed entry of CNI in children with renal impairment at the time of organ availability. There were no differences in renal function between pediatric patients with and without pre-LT renal impairment within the first year (cGFR: 135 mL/min/1.73 m2 vs. 144 mL/min/1.73 m2 ; p = 0.56) or at 5-8 yr following LT, (129 mL/min/1.73 m2 vs. 130 mL/min/1.73 m2 ; p = 0.97). In addition, there was no difference in ACR rates (50% vs. 43%, p = 0.62) between patients in the basiliximab group and those patients receiving standard CNI and steroid strategies. The utilization of a renal-sparing approach with basiliximab alongside delayed entry and lower early target trough levels of CNI in children with renal impairment at the time of LT is safe and maintains excellent long-term kidney function.

Interleukin-10 (IL-10) signaling genes are attractive inflammatory bowel disease (IBD) candidate genes as IL-10 restricts intestinal inflammation, IL-10 polymorphisms have been associated with IBD in genome-wide association studies, and mutations in IL-10 and IL-10 receptor (IL-10R) genes have been reported in immunodeficient children with severe infantile-onset IBD. Our objective was to determine if IL-10R polymorphisms were associated with early-onset IBD (EO-IBD) and very-early-onset IBD (VEO-IBD).Candidate-gene analysis of IL10RA and IL10RB was performed after initial sequencing of an infantile onset-IBD patient identified a novel homozygous mutation. The discovery cohort included 188 EO-IBD subjects and 188 healthy subjects. Polymorphisms associated with IBD in the discovery cohort were genotyped in an independent validation cohort of 422 EO-IBD subjects and 480 healthy subjects.We identified a homozygous, splice-site point mutation in IL10RA in an infantile-onset IBD patient causing a premature stop codon (P206X) and IL-10 insensitivity. IL10RA and IL10RB sequencing in the discovery cohort identified five IL10RA polymorphisms associated with ulcerative colitis (UC) and two IL10RB polymorphisms associated with Crohn's disease (CD). Of these polymorphisms, two IL10RA single nucleotide polymorphisms, rs2228054 and rs2228055, were associated with VEO-UC in the discovery cohort and replicated in an independent validation cohort (odds ratio [OR] 3.08, combined P = 2 x 10(-4); and OR 2.93, P = 6 x 10(-4), respectively).We identified IL10RA polymorphisms that confer risk for developing VEO-UC. Additionally, we identified the first splice site mutation in IL10RA resulting in infantile-onset IBD. This study expands the phenotype of IL10RA polymorphisms to include both severe arthritis and VEO-UC.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in adults and children and is currently the third most common indication for liver transplantation in North America. Its pathogenesis is thought to be secondary to multiple "hits" derived from the dietary components, adipose tissue, immune system, and intestinal microbiota. Lack of physical activity may contribute as well. Nutrients may exert their effect directly or through alteration of the intestinal microbiota. Research focusing on specific dietary components predisposing to NAFLD has shown conflicting results. Total energy intake, and macronutrients, has been linked to the development of NAFLD. Fructose not only contributes to hepatic steatosis but may trigger inflammatory signals as well. Polyunsaturated fatty acids are thought to exert anti-inflammatory effects. The role of vitamins as well as minerals in this field is actively being investigated. In this review, we discuss the evidence-linking macronutrients (such as carbohydrates and fat in general and fructose, fiber, short chain fatty acids, polyunsaturated fatty, and choline specifically) and micronutrients (such as vitamin E and C and minerals) with the development and treatment of NAFLD. We also discuss the literature on physical activity and NAFLD.